ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 155 citations in OpenAlex.
- Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease.Chemical reviews · 2026Review
- Revised Two-Stage Model of Preeclampsia Based on Autophagic Dysfunction: A Comprehensive Review.Biomolecules · 2026Review
- Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Bovine viral diarrhea virus suppresses type I IFN production by inducing MAVS degradation via autophagy mediated by the ROS-endoplasmic reticulum stress axis.Journal of virology · 2026Article
- The current status of Charcot-Marie-Tooth disease type 1 A treatment.Acta neurologica Belgica · 2025Review
- The role of thrombospondin-1 in trehalose-induced autophagy and ocular hypertension in mice.Scientific reports · 2025Article
- Sodium-Glucose Cotransporter-2 Inhibitor Enhances Hepatic Gluconeogenesis and Reduces Lipid Accumulation via AMPK-SIRT1 Activation and Autophagy Induction.Endocrinology and metabolism (Seoul, Korea) · 2025Article
- Unraveling the therapeutic landscape of approved non-peptide macrocycles.Acta pharmaceutica Sinica. B · 2025Review
- Inhibition of histone deacetylase 6 activity mitigates neurological impairment and post-hemorrhagic hydrocephalus after intraventricular hemorrhage by modulating pyroptosis and autophagy pathways.Fluids and barriers of the CNS · 2025Article
- MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Gynostemma pentaphyllum (Thunb.) Makino Affects Autophagy and Improves Diabetic Peripheral Neuropathy Through TXNIP-Mediated PI3K/AKT/mTOR Signaling Pathway.Applied biochemistry and biotechnology · 2025Article
- Psoralen-mediated regulation of osteogenic differentiation of periodontal ligament stem cells: involvement of the mTOR pathway.Frontiers in cell and developmental biology · 2025Article
- Astragaloside IV improves the survival rates of retinal ganglion cells in traumatic optic neuropathy by regulating autophagy mediated by the AMPK-MTOR-ULK signaling pathway.Molecular vision · 2025Article
- Lassa virus Z protein hijacks the autophagy machinery for efficient transportation by interrupting CCT2-mediated cytoskeleton network formation.Autophagy · 2024Article
- Phospholipase D Family Member 4 Regulates Microglial Phagocytosis and Remyelination via the AKT Pathway in a Cuprizone-Induced Multiple Sclerosis Mouse Model.CNS neuroscience & therapeutics · 2024Article
- Interactions Between Extracellular Vesicles and Autophagy in Neuroimmune Disorders.Neuroscience bulletin · 2024Review
- p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot-Marie-Tooth disease type 1A.Scientific reports · 2024Article
- Review
- Review
- Sensitive imaging of Endoplasmic reticulum (ER) autophagy with an acidity-reporting ER-Tracker.Autophagy · 2023Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Misexpression and cytosolic retention of peripheral myelin protein 22 (PMP22) within Schwann cells (SCs) is associated with a genetically heterogeneous group of demyelinating peripheral neuropathies. PMP22 overproducer C22 and spontaneous mutant Trembler J (TrJ) mice display neuropathic phenotypes and affected nerves contain abnormally localized PMP22. Nutrient deprivation-induced autophagy is able to suppress the formation of PMP22 aggregates in a toxin-induced cellular model, and improve locomotor performance and myelination in TrJ mice. As a step toward therapies, we assessed whether pharmacological activation of autophagy by rapamycin (RM) could facilitate the processing of PMP22 within neuropathic SCs and enhance their capacity to myelinate peripheral axons. Exposure of mouse SCs to RM induced autophagy in a dose- and time-dependent manner and decreased the accumulation of poly-ubiquitinated substrates. The treatment of myelinating dorsal root ganglion (DRG) explant cultures from neuropathic mice with RM (25 nm) improved the processing of PMP22 and increased the abundance and length of myelin internodes, as well as the expression of myelin proteins. Notably, RM is similarly effective in both the C22 and TrJ model, signifying that the benefit overlaps among distinct genetic models of PMP22 neuropathies. Furthermore, lentivirus-mediated shRNA knockdown of the autophagy-related gene 12 (Atg12) abolished the activation of autophagy and the increase in myelin proteins, demonstrating that autophagy is critical for the observed improvement. Together, these results support the potential use of RM and other autophagy-enhancing compounds as therapeutic agents for PMP22-associated demyelinating neuropathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.